The long term goal of the proposed research is to identify, and to characterize biochemically and biologically, putative CNS-derived neurotrophic agents that influence the survival and development of spinal motoneurons (MNS) in the chick embryo. By capitalizing on our prior work indicating that a protein(s) derived from chicken CNS can promote the in vitro and in vivo survival on MNS, we will attempt to isolate and identify this agent(s) using standard methods of protein chemistry. We will also examine the in vitro and in vivo effects of members of the NGF or neurotrophin family on MN survival (e.g., NGF, BDNF, NT-3, and possibly NT-4 and NT-5). Finally, we will examine the in vivo expression of mRNAs for suspected trophic agents and their receptors in the avian CNS using in situ hybridization methodology. These include: NGF, FGF, CNTF, S100, BDNF and NT-3. The major significance of these studies is that they represent the first attempt to demonstrate that putative CNS-derived neurotrophic agents can act in vitro and in vivo to promote the survival of a population of neurons (MNS) that are at risk in human motor neuron diseases.